Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) thought to result from the destruction of myelin by autoreactive T cells. CD4+ T cells characterized by the production of IFN-γ (Th1 cells) or IL-17 (Th17 cells) are considered important contributors to MS immunopathogenesis (Miossec et al., 2009; Sospedra and Martin, 2005; Steinman, 2014). FoxP3+ regulatory T cells (Tregs) and IL-10 secreting type 1 regulatory T cells (Tr1) regulate the activity of effector T cells, accordingly deficits in Tregs and Tr1 cells have been described in MS (Astier et al., 2006; Sakaguchi et al., 2010; Viglietta et al., 2004). Thus, the balance between effector and regulatory T cells controls MS disease activity (Miossec et al., 2009; Sospedra and Martin, 2005; Steinman, 2014).
Genetic polymorphisms have been associated with MS risk and/or pathogenesis (Beecham et al., 2013; Sawcer et al., 2011). However, environmental factors such as infections (Ascherio et al., 2001; Correale and Farez, 2007; Correale et al., 2006), sodium intake (Farez et al., 2014), smoking (Hernan, 2005) and vitamin D levels (Ascherio et al., 2014) also affect MS development and course. Lower levels of vitamin D, for example, are associated with higher relapse rates (Runia et al., 2012; Simpson et al., 2010). As a result of the regulation of its synthesis by sun exposure, a significant seasonal fluctuation on vitamin D levels is observed in most locations, with a peak in spring-summer and a nadir in autumn and winter (Rosecrans and Dohnal, 2014). Thus, based on the reported anti-inflammatory effects of vitamin D (Correale et al., 2009) (Ascherio et al., 2010), MS relapse occurrence is predicted to peak during autumn and winter. However, several studies, including a meta-analysis (Jin et al., 2000) and a recent multicentric study (Spelman et al., 2014) found that MS disease activity is higher in spring and summer, suggesting that additional factors play a role in MS relapse seasonality.